A catalytic-independent role for the LUBAC in NF-κB activation upon antigen receptor engagement and in lymphoma cells

Sonia M. Dubois, Catherine Alexia, Youtong Wu, Hélöise M. Leclair, Claire Leveau, Emilie Schol, Thierry Fest, Karin Tarte, Zhijian J. Chen, Julie Gavard, Nicolas Bidère

Research output: Contribution to journalArticle

63 Scopus citations

Abstract

Antigen receptor-mediated nuclear factor κB (NF-κB) activation relies on the formation of a large multi-protein complex that contains CARMA1, BCL10, and MALT1 (CBM complex). This signalosome is pirated in the activated B-cell-like subgroup of diffuse large B-cell lymphoma (ABCDLBCL) to drive aberrant NF-κB activation, thereby promoting cell survival and propagation. Using an unbiased proteomic approach, we screened for additional components of the CBM in lymphocytes. We found that the linear ubiquitin chain assembly complex (LUBAC), which was previously linked to cytokine-mediated NF-κB activation, dynamically integrates the CBM and marshals NF-κB optimal activation following antigen receptor ligation independently of its catalytic activity. The LUBAC also participates in preassembled CBM complex in cells derived from ABC DLBCL. Silencing the LUBAC reduced NF-κB activation and was toxic in ABC DLBCL cell lines. Thus, our findings reveal a role for the LUBAC during lymphocyte activation and in B-cell malignancy.

Original languageEnglish (US)
Pages (from-to)2199-2203
Number of pages5
JournalBlood
Volume123
Issue number14
DOIs
StatePublished - Apr 3 2014

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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    Dubois, S. M., Alexia, C., Wu, Y., Leclair, H. M., Leveau, C., Schol, E., Fest, T., Tarte, K., Chen, Z. J., Gavard, J., & Bidère, N. (2014). A catalytic-independent role for the LUBAC in NF-κB activation upon antigen receptor engagement and in lymphoma cells. Blood, 123(14), 2199-2203. https://doi.org/10.1182/blood-2013-05-504019